12-56042173-A-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001029.5(RPS26):c.3+4A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001029.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPS26 | NM_001029.5 | c.3+4A>C | splice_region_variant, intron_variant | Intron 1 of 3 | ENST00000646449.2 | NP_001020.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPS26 | ENST00000646449.2 | c.3+4A>C | splice_region_variant, intron_variant | Intron 1 of 3 | NM_001029.5 | ENSP00000496643.1 | ||||
RPS26 | ENST00000356464.10 | c.3+4A>C | splice_region_variant, intron_variant | Intron 2 of 4 | 1 | ENSP00000348849.5 | ||||
RPS26 | ENST00000552361.1 | c.3+4A>C | splice_region_variant, intron_variant | Intron 2 of 4 | 5 | ENSP00000450339.1 | ||||
RPS26 | ENST00000548590.1 | n.30+4A>C | splice_region_variant, intron_variant | Intron 1 of 2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151968Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251362Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135862
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461840Hom.: 0 Cov.: 35 AF XY: 0.0000289 AC XY: 21AN XY: 727222
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151968Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74226
ClinVar
Submissions by phenotype
Diamond-Blackfan anemia 10 Uncertain:1
Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 2042654). This variant has not been reported in the literature in individuals affected with RPS26-related conditions. This variant is present in population databases (rs201248213, gnomAD 0.02%). This sequence change falls in intron 1 of the RPS26 gene. It does not directly change the encoded amino acid sequence of the RPS26 protein. It affects a nucleotide within the consensus splice site. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at